AB0887 Designing a Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Investigate the Effect of Guselkumab Dosing Interval in Psoriatic Arthritis Patients with Inadequate Response to Tumor Necrosis Factor Inhibition
Authors: A. Ogdie, J. F. Merola, P. J. Mease, C. T. Ritchlin, J. U. Scher, D. Chan, S. D. Chakravarty, W. Langholff, O. Choi, Y. Krol, K. Rowland, A. B. Gottlieb
Journal: Annals of the Rheumatic Diseases (2022)

Background Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic therapy for patients (pts) with psoriatic arthritis (PsA), though a sizeable proportion of pts have an inadequate response (IR), and some may also have intolerance. Guselkumab (GUS), a human mAb that targets the IL-23 p19 subunit, provides an alternative mechanism of action to treat PsA. In the Phase 3 (Ph3) DISCOVER-1 study of GUS in active PsA, GUS every 4 weeks (Q4W) and Q8W clinical response rates were generally consistent between TNFi-naïve (263 pts) and TNFi-experienced (118 pts) cohorts. In the TNFi-experienced cohort and the limited number of DISCOVER-1 pts with IR to their prior TNFi (N=44), American College of Rheumatology 50% improvement (ACR50) and ACR70 response rates at W24 were numerically higher in GUS Q4W- than Q8W-treated pts. 1 Objectives To further investigate whether GUS Q4W could provide incremental benefit to some TNFi-IR PsA pts by analyzing the existing DISCOVER-1 dataset to facilitate the design of a new clinical trial. Methods Study feasibility assessments included comparison of key efficacy endpoints by treatment group at W24 among TNFi-experienced pts receiving GUS Q8W and Q4W in DISCOVER-1. Results from the DISCOVER-1 study also informed sample size power calculations for a primary endpoint of ACR20 response at W24 in a future study in a TNFi-IR PsA pt population. Results Comparison of several efficacy endpoints (ACR70 response, minimal disease activity, Investigator’s Global Assessment [IGA] of psoriasis 0/1 response) across treatment groups in the TNFi-experienced DISCOVER-1 cohort supports a potential dose response, with more frequent GUS administration eliciting numerically higher response rates (Table 1). A similar trend was observed for ACR20/50/70 responses in the smaller TNFi-IR population 1 , though these findings should be interpreted with caution due to limited sample size. ACR20 response rates at W24 of DISCOVER-1 were employed to estimate sample size requirements for a new study. Assuming comparable rates of GUS treatment effect seen in DISCOVER-1, a sample size of 150 randomized pts per group for PBO, GUS Q8W, and GUS Q4W would provide &gt;90% power to detect a significant difference between each GUS group and PBO for ACR20 response at W24. Based on these findings, a new Ph3b, multicenter, randomized, double-blind, PBO-controlled study, SOLSTICE, was designed to further evaluate the efficacy and safety of GUS in approximately 450 pts with active PsA who had IR to one prior TNFi, and to investigate the effect of GUS dosing interval in this important cohort of pts with PsA (Figure 1). Table 1. Clinical efficacy at W24 among DISCOVER-1 TNFi-experienced pts Placebo GUS Q8W GUS Q4W ACR20 17.9% (7/39) 56.1% (23/41) 57.9% (22/38) ACR50 5.1% (2/39) 26.8% (11/41) 34.2% (13/38) ACR70 2.6% (1/39) 2.4% (1/41) 21.1% (8/38) MDA 2.6% (1/39) 17.1% (7/41) 26.3% (10/38) IGA 0/1 a 7.7% (2/26) 48.3% (14/29) 67.9% (19/28) a IGA score of 0 (clear) or 1 (almost clear) among pts with ≥3% body surface area of psoriatic involvement and an IGA score ≥2 (mild-to-severe psoriasis) at baseline. ACR20/50/70, American College of Rheumatology 20%/50%/70% improvement; GUS, guselkumab; IGA, Investigator’s Global Assessment; MDA, minimal disease activity; Q4W, every 4 weeks; Q8W, every 8 weeks; TNFi, tumor necrosis factor inhibitor; W, week Conclusion PsA pts with TNFi-IR are typically difficult to treat. Overall data from the pivotal DISCOVER-1 study of GUS in pts with active PsA showed consistent clinical response between doses and between TNFi-naïve and TNFi-experienced pts. Analyses based on limited numbers of TNFi-experienced pts from DISCOVER-1 demonstrated potential incremental benefit for achievement of higher response criteria with more frequent dosing in some TNFi-IR pts. SOLSTICE, a Ph3b, randomized, placebo-controlled study, will test this hypothesis. References [1]Deodhar A, et al. Lancet. 2020;395:1115-1125. Figure 1. Disclosure of Interests Alexis Ogdie Shareholder of: Her husband has received royalties from Novartis, Consultant of: AbbVie, Amgen, BMS, Celgene, Corrona, Gilead, Global Health Living Foundation, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Abbvie, Pfizer and Novartis/Amgen to the University of Pennsylvania, Joseph F. Merola Paid instructor for: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Philip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Christopher T. Ritchlin Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, and Janssen, Grant/research support from: UCB Pharma, AbbVie, and Amgen, Jose U. Scher Consultant of: Janssen, Novartis, Pfizer, Abbvie, Sanofi, Kaleido and UCB Pharma, Grant/research support from: Novartis, Pfizer and Janssen (for investigator-initiated studies), Daphne Chan Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson &amp; Johnson, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson &amp; Johnson, Wayne Langholff Employee of: Janssen Research &amp; Development, LLC, and may own stock or stock options in Johnson &amp; Johnson, Olivia Choi Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson &amp; Johnson, Yevgeniy Krol Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson &amp; Johnson, Katelyn Rowland Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson &amp; Johnson, Alice B Gottlieb Consultant of: AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb Co., Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB Pharma, Dermavant, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB Pharma, Xbiotech, and Sun Pharma